Bisulfite‐free <i>PCDHGB7</i> methylation in urine enables early noninvasive detection of urothelial carcinoma

Urothelial carcinomas (UCs) are the fourth most common male malignancies. However, currently implemented detection methods for UC are usually invasive and/or show passable sensitivity and specificity. An accurate, practical, and effective approach is urgently needed for UC clinical detection. Based on the observation that <i>PCDHGB7</i> was hypermethylated in UC, we developed a bisulfite-free quantitative polymerase chain reaction (qPCR)-based <i>PCDHGB7</i> evaluation to enable urine for UC noninvasive detection. A total of 887 urine samples from UC/benign diseases of the urinary system (BUD) patients between 2022 and 2023 were included. All collected samples were divided into training and validation sets in a 2:1 ratio based on the order of patient enrollment. Results showed that hypermethylated <i>PCDHGB7</i> exhibited excellent sensitivity of 87.3% (95% CI: 80.7%-92.3%) and specificity of 91.0% (95% CI: 84.8%-95.3%) in efficiently distinguishing UC from BUD patients in the validation set, which is highly consistent with its performance in the training set. Moreover, <i>PCDHGB7</i> hypermethylation showed promising potential in identifying sessile UC tumors or cases that might be missed in clinical detection and outperformed standard urine cytology in detecting bladder cancer (82.1% vs. 34.5%), ureter cancer (78.1% vs. 34.4%), and renal pelvis cancer (90.9% vs. 22.7%). Overall, bisulfite-free qPCR-based <i>PCDHGB7</i> evaluation in urine provided a noninvasive, easy-to-perform, and effective way for UC early detection.